Powell Kristin Conrad, Damitz Robert, Chauhan Anuj
Department of Chemical Engineering, University of Florida, 1030 Center Drive, Gainesville, FL, 32611, United States.
Int J Pharm. 2017 Apr 15;521(1-2):8-18. doi: 10.1016/j.ijpharm.2017.01.058. Epub 2017 Feb 10.
We explore mechanisms of emulsion stability for several systems using Pluronic F68 and a range of oils commonly used in pharmaceutics and cosmetics. We report measurements of dynamic emulsion drop size, zeta potential, and creaming time, as well as dynamic interfacial tension and interfacial viscoelasticity. Experiments show that with 1wt% Pluronic F68, soybean oil emulsions were the most stable with no creaming over six months, followed by isopropyl myristate, octanoic acid, and then ethyl butyrate. The eventual destabilization occurred due to the rising of large drops which formed through Ostwald ripening and coalescence. While Ostwald ripening is important, it is not the dominant destabilization mechanism for the time scale of interest in pharmaceutical emulsions. The more significant destabilization mechanism, coalescence, is reduced through surfactant adsorption, which decreases surface tension, increases surface elasticity, and adds a stearic hindrance to collisions. Though the measured values of elasticity obtained using a standard oscillatory pendant drop method did not correlate to emulsion stability, this is because the frequencies for the measurements were orders of magnitude below those relevant to coalescence in emulsions. However, we show that the high frequency elasticity obtained by fitting the surface tension data to a Langmuir isotherm has very good correlation with the emulsion stability, indicating that the elasticity of the interface plays a key role in stabilizing these pharmaceutical formulations. Further, this study highlights how these important high frequency elasticity values can be easily estimated from surface isotherms.
我们使用普朗尼克F68以及一系列制药和化妆品中常用的油,探索了几种体系中乳液稳定性的机制。我们报告了动态乳液滴尺寸、zeta电位、乳析时间的测量结果,以及动态界面张力和界面粘弹性的测量结果。实验表明,添加1wt%的普朗尼克F68时,大豆油乳液最稳定,六个月内无乳析现象,其次是肉豆蔻酸异丙酯、辛酸,然后是丁酸乙酯。最终的不稳定是由于奥斯特瓦尔德熟化和聚并形成的大液滴上升所致。虽然奥斯特瓦尔德熟化很重要,但它不是药物乳液感兴趣的时间尺度上的主要失稳机制。更重要的失稳机制——聚并,通过表面活性剂吸附得以减少,表面活性剂吸附降低了表面张力,增加了表面弹性,并为碰撞增加了空间位阻。尽管使用标准振荡悬滴法测得的弹性值与乳液稳定性无关,这是因为测量频率比乳液中与聚并相关的频率低几个数量级。然而,我们表明,通过将表面张力数据拟合到朗缪尔等温线获得的高频弹性与乳液稳定性具有很好的相关性,这表明界面弹性在稳定这些药物制剂中起着关键作用。此外,这项研究突出了如何从表面等温线轻松估算这些重要的高频弹性值。